This application relates to a dialysis adapter cell and method of use, and especially relates to the use of the adapter cell in a United States Pharmacopoeia dissolution apparatus 4 for in vitro release testing of disperse dosage forms.
Drug delivery systems such as microspheres, liposomes, nanosuspensions, microemulsions, and the like have been the subject of significant research and development efforts. The advantages of these systems include the potential for controlled/modified delivery, targeted delivery, localized delivery, decreased dose, reduced toxicity, and protection of labile drugs (such as proteins) from degradation prior to and after administration. Several microsphere, nanosuspension, emulsion and liposome formulations have been approved by the United States Food and Drug Administration (FDA), and the number of such products is likely to increase rapidly with the advances in protein and gene therapeutics and the large number of new candidates with poor aqueous solubility.
In order to assure the performance and safety of these delivery systems, as well as to assist in the product development process, in vitro testing methods have been developed. In vitro release is an important indicator of in vivo product performance. Accordingly, in vitro release tests are used for routine assessment of process quality control, formulation optimization in product development, development of in vitro-in vivo relationships (IVIVR), and the like. In addition, in vitro release methods can also be applied for evaluation of scale-up and post approval changes (SUPAC), in cases where an approved IVIVR exists.
A variety of methods have been used for in vitro release testing of these drug delivery systems. Currently used methods for in vitro release testing from these dosage forms can be broadly divided into three categories: 1) membrane dialysis methods (such as dialysis sac, reverse dialysis sac, micro-dialysis, and Franz diffusion cells); 2) sample and separate methods (such as vial/tube/bottle methods with centrifugation or filtration after sampling); and 3) flow-through cell methods. These techniques are required to isolate the dosage form from the release medium for analytical purposes. None of these methods use an official United States Pharmacopoeia (USP) dissolution/release apparatus. In addition, the procedures and apparatuses used can vary among laboratories. Due to this lack of a standard method, results from different sources are usually not comparable. Moreover, some of the methods mentioned above are subject to high variability and have limitations, such as violation of sink conditions.
The lack of standard pharmacopoeial/regulatory tests for controlled release parenteral products is a major obstacle in the development and regulatory process of the products. In particular, the need for standards in in vitro release methods on colloidal disperse formulations like liposomes, microemulsions, nanosupsensions, or other like systems has not yet been met.